Oxidation Moffat-Pfitzner

The Oxidation of Some Carbohydrate Derivatives using Acetic Anhydride - Methyl Sulphoxide Mixtures and the Pfitzner-Moffat Reagent. Facile Synthesis of 3-Acetamido-3-deoxy-D-glucose and 3-Amino-3-deoxy-D-xylose, J. S. Brimacombe, J. G. H. Bryan, A. Husain, M. Stacey, and M. S. 

The synthesis of latanoprost (1) commences with the lactone 5 derived from the Corey lactone (Scheme I).11 12 The early introduction of the p-phenylbenzoyl protecting group12 in this lactone affords crystalline intermediates in the synthesis that are easy to handle and purify. In the next step, the primary alcohol functionality in the lactone 5 was oxidized using Pfitzner-Moffat conditions (DCC, DMSO and phosphoric acid) to yield the aldehyde 6. The crude aldehyde was then treated with dimethyl (2-oxo-4-phenyl)-phosphonate under Wadsworth-Emmons conditions (NaH, DME) to afford the enone 7 as a white crystalline solid in 59% yield. 

Oxidation of alcohols to aldehydes or ketone by DMSO activated with DCC (Pfitzner-Moffat), Ac2Q, (COCI)2, TFA, (Swem), P205l or pyridine-S03 (see 1sted). 

The oxidation of alcohols to carbonyl compounds is one of the most fundamental and important processes in the fine chemical industry. The classical methodology is based on the stoichiometric use of heavy metals, notably Cr and Mn (1,2). Alternatively metal-free oxidation, such as the Swern and Pfitzner-Moffat protocols, is based on e.g., dimethylsulfoxide as oxidant in the presence of an activating reagent such as N,N -dicyclohexylcarbodiimide, an acid anhydride or acid halide (3). Although the latter methods avoid the use of heavy metals, they usually involve moisture-sensitive oxidants and environmentally undesirable reaction media, such as chlorinated solvents. The desired oxidation of alcohols only requires the formal transfer of two hydrogen atoms, and therefore the atom economy of these methods is extremely disadvantageous. The current state of the art in alcohol oxidations... 

Whereas the original Moffat-Pfitzner oxidation employs dicyclohexylcarbodiimide to convert DMSO into the reactive intermediate DMSO species 1297, which oxidizes primary or secondary alcohols via 1298 and 1299 to the carbonyl compounds and dicyclohexylurea [78-80], subsequent versions of the Moffat-Pfitzner oxidation used other reagents such as S03/pyridine [80a, 83] or oxalyl chloride [81-83] to avoid the formation of dicyclohexylurea, which is often difficult to remove. The so-called Swern oxidation, a version of the Moffat-Pfitzner oxidation employing DMSO/oxalyl chloride at -60°C in CH2CI2 and generating Me2SCl2 1277 with formation of CO/CO2, has become a standard reaction in preparative organic chemistry (Scheme 8.31). 

FIGURE 2.19. Alternatives to DMSO in the Moffat-Pfitzner oxidation... 

The most utilized methods are the Pfitzner and Moffat reaction and its subsequent variations (Jones and Moffatt 1972). The oxidizing agent is dimethyl sulfoxide (DMSO). The generally accepted intermediate is structure 5.22 which leads to compound 5.23 by an elimination reaction (reaction 5.14). 

A new selective method of oxidizing alcohols was found by Pfitzner and Moffat.425 Treating primary or secondary alcohols with 2-5 moles of dicyclo-hexycarbodiimide (or related compounds such as diisopropylcarbodiimide) in anhydrous dimethyl sulfoxide containing 0.1-2 moles of H3P04 leads to aldehydes or ketones. The phosphoric acid can be replaced by pyridinium phosphite, cyanoacetate, hydrochloride, sulfate, or even phosphate the dimethyl sulfoxide may be diluted with 9 times its volume of an inert solvent. The reaction is carried out at 20° and sometimes gives superlative yields it is recommended particularly for steroid chemistry testosterone gives, e.g., 92% of 4-androstene-3,17-dione by this method. 

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